title: Novel roles of galectin-1 in hepatocellular carcinoma cell adhesion, polarization, and in vivo tumor growth.
abstract: Galectin-1 (Gal-1), a widely expressed β-galactoside-binding protein, exerts pleiotropic biological functions. Gal-1 is up-regulated in hepatocarcinoma cells, although its role in liver pathophysiology remains uncertain. We investigated the effects of Gal-1 on HepG2 hepatocellular carcinoma (HCC) cell adhesion and polarization. Soluble and immobilized recombinant Gal-1 (rGal-1) promoted HepG2 cell adhesion to uncoated plates and also increased adhesion to laminin. Antibody-mediated blockade experiments revealed the involvement of different integrins as critical mediators of these biological effects. In addition, exposure to rGal-1 markedly accelerated the development of apical bile canaliculi as shown by TRITC-phalloidin labeling and immunostaining for multidrug resistance associated-protein 2 (MRP2). Notably, rGal-1 did not interfere with multidrug resistance protein 1/P-glycoprotein or MRP2 apical localization, neither with transfer nor secretion of 5-chloromethylfluorescein diacetate through MRP2. Stimulation of cell adhesion and polarization by rGal-1 was abrogated in the presence of thiodigalactoside, a galectin-specific sugar, suggesting the involvement of protein-carbohydrate interactions in these effects. Additionally, Gal-1 effects were abrogated in the presence of wortmmanin, PD98059 or H89, suggesting involvement of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase and cyclic adenosine monophosphate-dependent protein kinase signaling pathways in these functions. Finally, expression levels of this endogenous lectin correlated with HCC cell adhesion and polarization and up-regulation of Gal-1-favored growth of hepatocarcinoma in vivo.
  
  
  CONCLUSIONS
  Our results provide the first evidence of a role of Gal-1 in modulating HCC cell adhesion, polarization, and in vivo tumor growth, with critical implications in liver pathophysiology.
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: María V
authors.initials: MV
authors.lastname: Espelt
authors.forename: Diego O
authors.initials: DO
authors.lastname: Croci
authors.forename: María L
authors.initials: ML
authors.lastname: Bacigalupo
authors.forename: Pablo
authors.initials: P
authors.lastname: Carabias
authors.forename: Malena
authors.initials: M
authors.lastname: Manzi
authors.forename: María T
authors.initials: MT
authors.lastname: Elola
authors.forename: Marina C
authors.initials: MC
authors.lastname: Muñoz
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Dominici
authors.forename: Carlota
authors.initials: C
authors.lastname: Wolfenstein-Todel
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.forename: María F
authors.initials: MF
authors.lastname: Troncoso
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000502:physiology*; D049109:Cell Proliferation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D037483:Galectin 1 / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000503:physiopathology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D037483:Galectin 1; D020928:Mitogen-Activated Protein Kinases; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019869:Phosphatidylinositol 3-Kinases; C000715087:ABCC2 protein, human